Copper-Catalysed Aminoboration of Vinylarenes with Hydroxylamine Esters - A Computational Mechanistic Study.

This first comprehensive computational study of the copper-mediated formal aminoboration utilising an electrophilic strategy has identified the most accessible pathway for the productive catalysis. The mechanistic picture derived from smooth energy profiles acquired by employing a reliable computational protocol applied to a realistic catalyst model conforms to all available experimental data. The high degree of chemo- and stereoselectivity achieved in syn-borylcupration and Umpolung electrophilic amination is instrumental to the exclusive generation of the (syn)-beta-aminoalkylborane product. On the one hand, syn-borylcupration furnishes exclusively beta-borylalkylcopper nucleophile upon boryl addition onto the vinylarene beta-carbon. Its subsequent approach by the hydroxylamine electrophile to deliver the product with the release of {P^P}CuI benzoate favours a stepwise stereoretentive SN2-type oxidative addition/N-C bond forming reductive elimination sequence. The benzoatecopper represent the catalyst resting state and its transformation into the catalytically competent borylcopper upon salt metathesis with Li(OtBu) base and transmetalation with B2pin2 is turnover limiting. Electronically modified beta-alkylstyrenes featuring a para-CF3 substituted phenyl ring render the borylcupration faster, whilst more electron-rich hydroxylamine agents decelerate the electrophilic amination.